PROJECT SUMMARY/ABSTRACT ? OVERALL The Fox Chase Cancer Center (FCCC), now in its 51st year as an NCI-designated Comprehensive Cancer Center, has undergone a profound transformation since the time of the last CCSG grant review. In 2012, Fox Chase entered into an affiliation with the Temple University Health System, creating a unique new model that combines the flexibility of a free-standing cancer center with the scientific and clinical breadth of a university- based matrix center. In addition to this organizational change, in 2013, FCCC came under new leadership with the appointment of Richard I. Fisher, MD as President and CEO of FCCC and Cancer Center Director. As a result of these developments, the size and scope of the Cancer Center have greatly expanded, both in terms of its scientific enterprise and also in the number and diversity of the patients served. Cancer-focused, Temple faculty members have been thoroughly integrated into FCCC, adding 54 new CCSG members, including three in leadership positions (Jean-Pierre Issa, MD, PhD, Co-Program Leader for Cancer Epigenetics; Susan Fisher, PhD, Associate Director for Population Science; Grace Ma, PhD, Director of Community Based Research). In addition to expanding membership, the affiliation has enabled access to specialized expertise at Temple University, including the Fels Institute for Cancer Research and Molecular Biology, the Moulder Center for Drug Discovery, and the newly created School of Public Health. Importantly, with the affiliation, FCCC now has greatly enhanced access to an underserved population within its catchment area, surrounding the Temple University Health Science Center in North Philadelphia. Other important accomplishments within the last grant cycle include: a) Recruitment of Wafik El-Deiry, MD, PhD to a new Deputy Directorship for Translational Research to enhance the clinical translation of basic research findings; b) A 40% increase in the direct costs of funded research at FCCC from 2013 - 2015 ($27.7M to $38.7M); c) 43-fold return on investment from CCSG- supported pilot projects; d) Increased accrual to treatment interventional trials, from 358 in 2011 to 668 in 2014 (an 87% increase); e) Establishment of a cutting-edge Research Program in Cancer Epigenetics; and f) Publication of more than 2,200 papers from 2011-2015, with strong intra- and inter-programmatic collaboration, including 20% in journals with Impact Factors > 8, and 11% in journals with Impact Factors > 10. These positive developments demonstrate the renewed strength of FCCC and the importance of its role in the care of cancer patients in this region.